The objective of this research is to elucidate the genes, cells, and mechanisms involved in the regulation of natural cell-mediated cytotoxicity (NCMC). We will examine in the mouse both non-H-2 and H-2 genetic control of NCMC using congenic and recombinant inbred strains of mice. Gene complementation will be investigated in one system. An optimal protocol for in vivo and in vitro augmentation of NCMC will be established and applied in genetic analyses. The cellular requirements and characteristics of in vitro activation and suppression of NCMC will be investigated. Methods for selectively depleting or isolating natural killer (NK) cells will be developed so that NK cells can be added or removed from cultures in studies of the NK cell's role in T and B cell immune responses. Conventional antibodies and monoclonal antibody-producing hybrid cell lines specific for NK-cell associated antigens will be generated for this purpose. A nonhuman primate model for NCMC will be investigated. Family and in vivo augmentation studies will be performed. The characteristics of the primate NK cell and the specificity of NCMC against nonhuman lymphoblastoid cell lines will be investigated.